Добавил:
Sekretar
kiopkiopkiop18@yandex.ru
t.me/Prokururor I Вовсе не секретарь, но почту проверяю
Опубликованный материал нарушает ваши авторские права? Сообщите нам.
Вуз:
Предмет:
Файл:Ординатура / Хирургия / Библиотека им академика М.И. Перельмана / Книга_5221_Библиотеки_им_академика_М_И_Перельмана.pdf
Infectious Disease and Neurocognition
Hysteria- like and psychosis- like symptoms
in people with encephalitis lethargica
e psychiatric phenomena of chronic encephalitis lethargica and their sometime
sensitivity to situational and emotional factors invited comparisons with hysteria.
Many of the hallmarks of hysteria— certain extrapyramidal motor phenomena,
autonomic nervous system symptoms, abnormal sleep- related states, altered sensibility, and even the triggering or abolition of contractions by touching “ovarian
points”— were also seen in encephalitis lethargica (Jakob, 1923, pp. 389– 390;
Schilder, 1922; Truelle & Petit, 1922), and the implications of these parallels were
vigorously debated between 1926 and 1936, primarily in France and Romania. One
side argued that encephalitis lethargica suggested that at least the predisposition to
hysteria involved the basal ganglia or the mesencephalon; the other, led by French
neurologist Joseph Babinski, countered that genuine hysteria by denition had no
neurologic basis, distinguishing it from the pseudo- hysteria of encephalitis lethargica. Interest in hysteria had generally ebbed by the end of the 1930s, and the debate
died without reaching a rm conclusion (see, for instance, Froment, 1937; Imbert,
1931; Marinesco, 1936; Radovici, 1937; van Bogaert, 1935).
Two symptoms described in encephalitis lethargica suggested that it might provide clues about the neuropathology of psychosis: catatonia and hallucinations.
Catatonia was more frequent during acute than chronic encephalitis lethargica, and
even then it was transitory and less intractable to inuence than in people with schizophrenia. Further, people with encephalitis lethargica were frustrated by catatonia,
unlike those with psychosis, and their personality was largely intact. In chronic
encephalitis lethargica, catatonic symptoms probably reected the reduced spontaneity associated with bradyphrenia. e critical dierences led to the view that
“catatonia” was neither specic to schizophrenia nor adequately circumscribed as
a symptom (de Wilde, 1959; Epstein & Young, 1929; Geimanovich, 1927; Padéano,
1923; Truelle & Petit, 1922).
Visual hallucinations, more frequent during chronic than acute encephalitis lethargica, were generally recognized to be delusions, whether mischievous, friendly,
or threatening; some patients calmly reported visions of animals or strange people,
mostly toward the end of the day, as if they were plays or lms, while others experienced only vague misperceptions in their peripheral vision (Kleist, 1926; Leonhard,
1932; Leyser, 1925; Lhermitte, 1932; McCowan & Cook, 1928a). As the hallucinations
were rather simple and stereotyped, some authors preferred the term “hallucinosis,”
similar to the nebulous visions even healthy people can have just before falling sleep
and those of the recently described “infundibular syndrome,” caused by tumors adjacent to the third ventricle and also including abnormalities of sleep, behavior, and
instinct as symptoms (Claude & Lhermitte, 1917). Most people could not direct
their hallucinations, but one of the patients described by Oliver Sacks banned his to a
blank television screen before ordering a painting (of a shanty town) specically for
Encephalitis Lethargica 19
the same purpose; he scheduled a hallucinosis session for aer lunch each day until
treatment with L- DOPA removed his control (Sacks, 1991, p. 214).
Aural hallucinations were rare, olfactory and tactile hallucinations quite unusual,
and their illusory nature was generally clear. Related phenomena included partial
optic agnosia, “derealization” (during which everything appeared “as though dead,
fallen asleep, alien”), the impression of leaving one’s body, and distorted time perception. Delusions of thought transference and mind- reading were oen reported,
as were hallucinations related to paresthesias (e.g., of poisoning or the presence of
animals inside one’s body), but major abnormal thought complexes (physical transformation, visions of the end of the world, paranoia) were uncommon (de Morsier,
1931; Jellie, 1927a; Neustadt, 1927; van der Scheer, 1936). “Incontinent nostalgia”
aer decades of chronic encephalitis lethargica— pleasant indulgence in memories
from the time they initially fell ill— was described (Sacks, 1991, pp. 74– 87).
e hallucinations of chronic encephalitis lethargica were quite dierent in nature to those of schizophrenia, and they were not accompanied by the negativism or
autism of psychosis (de Morsier, 1931; Leyser, 1924; Schilder, 1929). Nevertheless,
as parkinsonism could emerge even decades aer the acute illness, probable encephalitis lethargica during the mid- 1920s was sometimes identied in the medical histories of people with “schizophrenia” who developed parkinsonism as late
as the 1950s (Davison & Bagley, 1969; Lemke, 1950). Conversely, chronic encephalitis lethargica occasionally ameliorated or even extinguished psychotic symptoms
(but not personality- related symptoms) in people with schizophrenia (e.g., Dretler,
1935). In any case, the prevalence of psychosis- like conditions among people with
chronic encephalitis lethargica was quite low, no higher than 1– 2 percent (Stern,
1928, p. 228).
Conclusion
Encephalitis lethargica was the neuropsychiatric disorder par excellence, reinvigorating the search for the neurobiological bases of mental processes and psychiatric
disorders. As von Economo noted, “what has most astonished us as psychiatrists
is that in cases of encephalitis lethargica, in which we can localize the disease process to the basal ganglia and midbrain area . . . we nd a multitude of symptoms
we formally regarded as purely psychological processes, and which we mainly knew
from the severe psychoses . . . What strikes the observer most is a lack of aect and
apathy, together with a loss or at least marked decline in all psychomotor initiative
and mental activity” (1923, p. 40). e most obvious symptom of chronic encephalitis lethargica was post- encephalitic parkinsonism, but its mental and psychiatric
features— particularly bradyphrenia, loss of drive and impaired volition, and behavioral changes— were as crucial to the patient, who indeed oen regarded them as
more onerous than their motor problems. e complex neuropsychiatric phenomenon of the oculogyric crisis, as well as less frequent hysteria- and psychosis- like
Infectious Disease and Neurocognition
symptoms, suggested that subcortical brain structures played critical but hitherto
unrecognized roles in processes of personality and cognition.
References
ALBERT, M. L., FELDMAN, R. G. & WILLIS, A. L. 1974. e “subcortical dementia” of progressive
supranuclear palsy. J Neurol Neurosurg Psychiatry, 37, 121– 130.
AUDEN, G. A. 1925. Encephalitis lethargica— Its psychological implications. J Ment Sci, 71, 647– 658.
BENEDEK, L. 1925. Zwangsmäßiges Schreien in Anfällen als postencephalitische Hyperkinese. Z
Gesamte Neurol Psychiatr, 98, 17– 26.
BOND, E. D. & APPEL, K. E. 1931. e Treatment of Behavior Disorders Following Encephalitis: An
Experiment in Re- Education. New York: Commonwealth Fund.
BONHOEFFER, K. 1922. Psychische Residuärzustände nach Encephalitis Epidemica Bei Kindern.
Klin Wochenschr, 1, 1446– 1449.
BORTHWICK, G. 1926. Some observations on the aer- eects of encephalitis lethargica in children.
In: Metropolitan Asylums Board, Annual Report for the Year 1927. London: Harrison and Sons, pp.
148– 167.
BOSTROEM, A. 1930. Die psychischen Folgeerscheinungen der epidemischen Enzephalitis. Allg Z
Psychiatr Psychisch Gerichtl Med, 93, 417– 434.
BYCHOWSKI, G. 1923. Psychopathologische Untersuchungen über die Folgezustände nach der
Encephalitis epidemica. Z Gesamte Neurol Psychiatr, 83, 201– 246.
CALLIGARIS, G. 1926. La Neurastenia Postencefalitica. Milan: Istitituto Editoriale Scientico.
CHŁOPICKI, W. 1931. Über anfallweise auretende Zwangserscheinungen im Verlaufe von
Parkinsonismus nach der epidemischen Encephalitis. Arch Psychiatr Nervenkr, 93, 1– 27.
CHODOS, C. G. 1933. Zur Psychopathologie des chronischen Stadiums der Encephalitis lethargica. Z
Gesamte Neurol Psychiatr, 145, 593– 597.
CLAUDE, H. & LHERMITTE, J. 1917. Le syndrome infundibulaire dans un cas de tumeur du troisième
ventricule. Presse Méd, 41, 417– 418.
DAVISON, K. & BAGLEY, C. R. 1969. Schizophrenia- like psychoses associated with organic disorders
of the central nervous system: A review of the literature. In: R. N. HERRINGTON (Ed.), Current
Problems in Neuropsychiatry: Schizophrenia, Epilepsy, the Temporal Lobe. Ashford: Headley Bros for
the Royal Medico- Psychological Association.
DAWSON, S. & CONN, J. 1931. Intelligence and Disease: A Survey of Glasgow Children. London: His
Majesty’s Stationery Oce.
DE MORSIER, G. 1931. L’importance des troubles mentaux et nerveux postencéphalitiques pour la
nosologie et la pathogénie des psychoses et des névroses. Arch Suisses Neurol Psychiatr, 27, 125– 136.
DE WILDE, J. A. 1959. Over Organische Defectpsychosen: Een Klinisch- Psychiatrisch Onderzoek naar
het Voorkomen van Gevolgtoestanden van Encephalitis Lethargica. Amsterdam: Van Gorcum.
DELATER, G. 1920. Auto observation d’encephalite lethargique. Paris Med, 37, 316– 319.
DELATER, G. 1948. Suite sur trente ans et n d’une auto- observation d’encéphalite léthargique. Paris
Med, 38, 229– 230.
DELBEKE, R. & VAN BOGAERT, L. 1928. Le Probleme General des Crises Oculogyres au Cours de
L’encephalite Epidemique Chronique. Paris: Doin.
DRETLER, J. 1935. Inuencé de l’encéphalite épidémique chronique sur la schizophrénie. L’Encéphale,
30, 656– 670.
EBAUGH, F. G. 1923. Neuropsychiatric sequelae of acute epidemic encephalitis in children. Am J Dis
Child, 25, 89– 97.
EPSTEIN, J. & YOUNG, J. L. L. 1929. Similarities involved in the production of the catatonia of de-
mentia præcox and the Parkinsonian syndrome of encephalitis. US Vet Bur Med Bull, 5, 843– 849.
EWALD, G. 1925. Schauanfälle’ als postencephalitische Störung. (Zugleich ein Beitrag zur Frage
psychischer Störungen bei postencephalitischen Zuständen). Monatsschr Psychiatr Neurol, 57, 222– 253.
Encephalitis Lethargica 21
FINDLAY, L. & SHISKIN, C. 1921. Epidemic encephalitis (encephalitis lethargica) in childhood: With
special reference to the changes in the cerebro- spinal uid. Glasgow Med J, 95, 18.
FLECK, U. 1927. Über die psychischen Folgezustände nach Encephalitis epidemica bei Jugendlichen.
Arch Psychiat Nervenkr, 79, 723.
FLECK, U. 1930. Psychiatrische Beobachtungen bei nichtgeisteskranken Postencephalitikern.
Psychiatr- Neurol Wochenschr, 32, 498– 500.
FLECK, U. 1933. Über Selbstmorde und Selbstmordversuche bei Postencephalitikern mit Bemerkungen
über die Persönlichkeitsänderung der erwachsenen parkinsonistischen Postencephalitiker. Arch
Psychiatr Nervenkr, 99, 233– 300.
FOLEY, P. B. 2012. e encephalitis lethargica patient as a window on the soul. In: L. S. JACYNA & S.
T. CASPER (Eds.), e Neurological Patient in History. Rochester, NY: University of Rochester Press,
pp. 184– 211.
FOLEY, P. B. 2017. Encephalitis Lethargica: e Mind and Brain Virus. New York: Springer.
FROMENT, J. 1937. L’accident hystérique pithiatique et la physio- pathologie dite hystérique. Rev
Neurol, 67, 153– 195.
GEIMANOVICH, A. I. 1927. Psihotičeskoe Soderžanie Èpidemičeskogo Èncefalita. In: A. I. GEIMANOVICH
(Ed.) Infekcii i Nervnaja Sistema. Charkov: Vseukrainskoe Medicinskoe Izdatel'stvo Naučnaja Mysl’, pp.
105– 116.
GERSTMANN, J. & KAUDERS, O. 1924. Über den Mechanismus der postencephalitischen
“psychopathieähnlichen” Zustandsbilder bei Jugendlichen. Arch Psychiatr Nervenkr, 71, 165– 182.
GOODHART, S. & SAVITSKY, N. 1933. Self- mutilation in chronic encephalitis avulsion of both eye-
balls and extraction of teeth. J Nerv Ment Dis, 78, 652.
HALL, A. J. 1939. Mental accompaniments of epidemic encephalitis. In: R. G. Gordon (Ed.), A Survey
of Child Psychiatry. London: Oxford University Press, pp. 17– 27.
HAUPTMANN, A. 1922. Der “Mangel an Antrieb”— von innen gesehen (Das psychische Korrelat der
Akinese). Arch Psychiatr Nervenkr, 66, 615– 686.
HESNARD. 1920. La psycho- encéphalite aiguë epidémique et les troubles psychiques de l’encéphalite
aiguë dite léthargique. L’Encéphale, 15, 443– 454.
HOFSTADT, F. 1921. Über Spät- und Dauerschäden nach Encephalitis epidemica im. J P edi at r, 29, 272.
HOFSTADT, F. 1923. Über die Spätschäden der Epidemischen Encephalitis im Kindesalter. Klinische
Wochenschri, 2, 1759– 1761.
HOMBURGER, A. 1926. Psychopathieähnliche Veränderungen bei Kindern im Gefolge der
epidemischen Enzephalitis. In: Vorlesungen über Psychopathologie des Kindesalters. Berlin: Springer,
pp. 451– 462.
HYMAS, N., LEES, A., BOLTON, D., EPPS, K. & HEAD, D. 1991. e neurology of obsessional slow-
ness. Brain, 114 (Pt 5), 2203– 2233.
IMBERT, P. 1931. Le problème de l’hystérie dans le passé et en face des états striés post encéphalitiques.
èse présentée à la Faculté de médecine de Lyon. Lyon: Bosc frères, M. et L. Riou.
JACOB- KLEFFNER, E. 1934. Über pathologische Neugier und Mangel an Langeweile bei Encephalitis
epidemica. Arch Psychiatr Nervenkr, 101, 657– 665.
JAKOB, A. 1923. Die extrapyramidalen Erkrankungen: Mit besonderer Berücksichtigung der pathologischen
Anatomie und Histologie und der Pathophysiologie der Bewegungsstörungen. Berlin: Springer.
JELLIFFE, S. E. 1927a. e mental pictures in schizophrenia and in epidemic encephalitis: eir alli-
ances, dierences and a point of view. Am J Psychiatry, 83, 413– 465.
JELLIFFE, S. E. 1927b. Postencephalitic Respiratory Disorders: Review of Syndromy, Case Reports,
Physiopathology, Psychopathology and erapy. New York: Nervous and Mental Disease Publishing
C omp an y.
JELLIFFE, S. E. 1932. Psychopathology of Forced Movements and the Oculogyric Crises of Lethargic
Encephalitis. New York: Nervous and Mental Disease Publishing Company.
KEHRER, F. 1938. Die Verbindung von chorea- und ticförmigen Bewegungen mit Zwangsvorstellungen
und ihre Beziehungen zu den Zwangsvorgängen bei Zwangsneurose und Encephalitis epidemica.
Basel: Karger Publishers.
KIRSCHBAUM, M. 1921. Über Persönlichkeitsveränderungen bei Kindern infolge von epidemischer
Encephalitis. Z Gesamte Neurol Psychiatr, 73, 599– 605.
Infectious Disease and Neurocognition
KLEIST, K. 1926. Episodische Dämmerzustände: ein Beitrag zur Kenntnis der konstitutionellen
Geistesstörungen. Leipzig: ieme.
KRAMER, F. & POLLNOW, H. 1932. Über eine hyperkinetische Erkrankung im Kindesalter. Eur
Neurol, 82, 1– 20.
LANGE, W. 1934. Erfahrungen und Ergebnisse auf Grund einer zehnjährigen Beobachtung in der
Encephalitiker- Abteilung Chemnitz- Altendorf. Zeitschr Kinder, 43, 263– 299.
LEMKE, R. 1950. Über die symptomatische Schizophrenie. Arch Psychiatr Nervenkr, 185, 756– 772.
LEONHARD, K. 1932. Besonderheiten an den halluzinatorisch- paranoiden Bildern nach epidemischer
Encephalitis. Z Gesamte Neurol Psychiatr, 138, 780– 807.
LEYSER, E. 1924. Untersuchungen über die Charakterveränderungen nach Encephalitis epidemica.
Arch Psychiatr Nervenkr, 72, 552– 609.
LEYSER, E. 1925. Zur dierentialdiagnose metencephalitischer und schizophrener störungen. Z
Gesamte Neurol Psychiatr, 99, 424– 452.
LHERMITTE, J. 1932. Sur la régulation des fonctions corticales. Le mésocéphale, organe régulateur.
L’Encéphale, 27, 757– 785.
MÄKELÄ, V. 1923. Über psychische Störungen bei und nach der epidemischen Encephalitis: Aus der
psychiatr. Helsinki: Klinik zu Helsinki.
MAKOWSKI, J. H. 1983. Contribution à l’Étude des Malades Mentaux Dangereux: Itinéraire Médico-
Légal et Psychiatrique de 1926 à 1982 d’un Malade Présentant des Séquelles d’Encéphalite Epidémique,
ou Maladie de Von Economo- Cruchet. Paris: esis.
MARINESCO, G. 1936. Contribution à l’étude de l’association de l’encéphalite épidémique et des
troubles hystériformes. Folia Neuropathol Est, 15/ 16, 175– 192.
MARINESCO, G., RADOVICI, A. & DRAGANESCO, S. 1925. Accès paroxystiques hypertoniques
de déviation conjuguée de la tête et des yeux au cours du parkinsonisme post- encéphalitique. Rev
Neurol (Paris), 33, 148– 59.
MAYER- GROSS, W. & STEINER, G. 1921. Encephalitis lethargica in der Selbstbeobachtung. Z Ges
Neurol Psychiat, 73, 283.
MCCOWAN, P. & COOK, L. 1928a. e mental aspect of chronic epidemic encephalitis. Lancet, 211,
1316– 1320.
MCCOWAN, P. & COOK, L. 1928b. Oculogyric crises in chronic epidemic encephalitis. Brain, 51, 285– 309.
MEDICAL CORRESPONDENT. 1924. ‘Sleepy sickness.’ A disease which makes criminals. Tim es, 20
August, 7D.
MENGER, P. 1929. Les Perversions Morales Postencéphalitiques. Paris: Éditions Médicales Norbert
Maloine.
MINISTRY OF HEALTH 1924. Memorandum on Encephalitis Lethargica. London: His Majesty’s
Stationery Oce.
NAVILLE, F. 1922. Etudes sur les complications et les sequelles mentales de l’encephalite epidemique.
La bradyphrenie. L’Encephale, 17, 369– 375.
NAVILLE, F. 1924. Les centres psychiques sous- corticaux paléencéphaliques. Réexions à propos de la
déchéance mentale post- encéphalitique. Arch Psychol, 19, 38– 44.
NEUSTADT, R. 1927. Zur Auassung der Psychosen bei Metencephalitis. Arch Psychiatr Nervenkr, 81,
99– 132.
NEUSTADT, R. 1932. Die chronische Encephalitis epidemica in ihrer gutachtlichen und sozialen
Bedeutung. Leipzig: Johann Ambrosius Barth.
NOVELLI, J. B. & QUAGLIOTTI, J. N. 1929. Las bradiestesias postencefaliticas; la viscosidad
psicosensorial y sensitiva. Actas de la Conferencia Latino- Americana de Neurología, Psiquiatría y
Medicina Legal, 1, 609– 611.
ONUAGULUCHI, G. 1961. Crises in post- encephalitic Parkinsonism. Brain, 84, 395– 414.
PADÉANO, G. 1923. Sur le syndrome hébéphréno- catatonique dans l’encéphalite épidémique et les argu-
ments qu’on peut en tirer en faveur de la pathogénie de la démence précoce. Paris: Ollier- Henry.
PARSONS, A. C. 1928. Report of an Inquiry into the Aer- Histories of Persons Attacked by Encephalitis
Lethargica. London: His Majesty’s Stationery Oce.
PAULIAN, D. & STANESCO, J. 1932. Contribution à l’étude des troubles mentaux dans le
Parkinsonisme. Ann Méd- Psychol, 90, 392– 400.
Encephalitis Lethargica 23
RADOVICI, A. 1937. La conception actuelle de l’hystérie. Sem Hop Paris, 18, 493– 503.
ROYAL SOCIETY OF MEDICINE. 1925. Sections of Psychiatry, Neurology, Study of Disease in
Children, and Epidemiology, Joint Discussion No. 2: Discussion on the mental sequelae of encephalitis lethargica. Proc R Soc Med, 18, 17– 39.
RUNGE, W. 1928. Psychosen bei gehirnerkrankungen. In: O. BUMKE (Ed.), Die exogenen
Reaktionsformen und die organisicheen Psychosen (Handbuch der Geisteskrankheiten. 7. Band.
Spezieller Teil III). Berlin: Julius Springer, pp. 526– 680.
SACKS, O. 1991. Awakenings (Rev. ed.). London: Picador/ Pan Macmillan.
SCHILDER, P. 1922. Einige Bemerkungen zu der Problemsphäre: Cortex, Stammganglien. Z Gesamte
Neurol Psychiatr, 74, 454– 481.
SCHILDER, P. 1929. Zur Kenntnis der Psychosen bei chronischer Encephalitis epidemica. Nebst
Bemerkungen über die Beziehung organischer Strukturen zu den psychischen Vorgängen. Z
Gesamte Neurol Psychiatr, 118, 327– 345.
SLOW, E. J. & LANG, A. E. 2017. Oculogyric crises: A review of phenomenology, etiology, pathogen-
esis, and treatment. Mov Disord, 32, 193– 202.
SORIANO, J. B., MURTHY, S., MARSHALL, J. C., RELAN, P. & DIAZ, J. V. 2022. A clinical case deni-
tion of post- COVID- 19 condition by a Delphi consensus. Lancet Infect Dis, 22, e102– e107.
STALLYBRASS, C. O. 1926. Encephalitis lethargica in childhood. Child, 17, 33– 38.
STECK, H. 1931. Les syndromes mentaux postencéphalitiques. Zurich: Orell Fuessli.
STERN, F. 1924. Die epidemische Encephalitis und ihre soziale Bedeutung. Zeitschri für
Medizinalbeamte und Krankenhausärzte, 37, 399– 427.
STERN, F. 1927. Über psychische Zwangsvorgänge und ihre Entstehung bei encephalitischen Blickkrämpfen,
mit Bemerkungen über die Genese der encephalitischen Blickkrämpfe: Zusammengestellt aus Vorträgen in
der Med. Gesellscha Göttingen am 2. VI. 1927 und auf der Jahresvers. des Dtsch. Vereins f. Psych. in Wien.
Arch Psychiatr Nervenkr, 81, 522– 560.
STERN, F. 1928. Die Epidemische Encephalitis. Berlin: Julius Springer.
THIELE, R. 1926. Zur Kenntnis der psychischen Residuärzustände nach Encephalitis epidemica
bei Kindern und Jugendlichen, insbesondere der weiteren Entwicklung dieser Fälle. Basel: Karger
Publishers.
TRUELLE, V. & PETIT, G. 1922. Les troubles mentaux dans l’Encéphalite Epidémique. Congrès des
Aliénistes et neurologistes de France et des pays de langue française, Quimper: 1922. Paris: Masson.
VAN BOGAERT, L. 1935. L’hystérie et les fonctions diencéphaliques, étude neurologique. In Comptes
rendus: Congrès des médecins aliénistes et neurologistes de France et des pays de langue française,
XXXIXe session, Bruxelles (22– 28 juillet 1935), pp. 169– 277.
VAN BOGAERT, L. & DELBEKE, R. 1926. Contagion des crises oculogyres chez des Parkinsoniens
postencéphalitiques. Nouvelle observation de blépharotonie encéphalitique. États aectifs et etats
toniques. J Neurol Psychiatr, 26, 269– 280.
VAN DER SCHEER, W. M. 1936. Psychopathologische en psychotische verschijnselen bij en na en-
cephalitis epidemica. Psychiatr Neurol Bladen, 40, 518– 534.
VON ECONOMO, C. 1923. Encephalitis lethargica. Verh Dtsch Ges Inn Med, 35, 10– 44.
VON ECONOMO, C. 1931. Encephalitis Lethargica: Its Sequelae and Treatment. London: Oxford
University Press.
VON THURZÓ, E. & KATONA, T. 1927. Über die Benedeksche Klazomanie und die Sonquessche
Palilalie, als postenkephalitische Hyperkinesen. Dtsch Z Nervenheilkd, 98, 278– 283.
WALUSINSKI, O. 2022. A history of oculogyric crises during the encephalitis lethargica pandemic.
Rev Neurol, 178, 878– 885.
WILSON, W. P., HOHMAN, L. B. & ODOM, G. L. 1952. Treatment of behavior disorders incidental to
organic cerebral disease by prefrontal lobotomy; report of seven cases. Dis Nerv Syst, 13, 274– 277.
WIMMER, A. 1930. Zur Kriminalität der Encephalitiker. Acta Psychiatr (Københ), 5, 23.
WORLD HEALTH ORGANIZATION 1992. e ICD- 10 Classication of Mental and Behavioural
Disorders. Geneva: World Health Organization.
WORLD HEALTH ORGANIZATION 2022. Impulse Control Disorders. Geneva: World Health
Organization.
ZINGERLE, H. 1936. Über subcorticale Anfälle. Dtsch Z Nervenheilkd, 140, 113– 168.
2
The Associations Between Herpes
Simplex Virus and Neurocognitive and
Neuropsychiatric Disorders
Guy D. Eslick
Introduction
A member of the Herpesviridae family of viruses (Banerjee et al., 2020), herpes simplex virus (HSV) consists of two subtypes, HSV- 1 and HSV- 2, which are also known
as human alphaherpesvirus- 1 and human alphaherpesvirus- 1, respectively. HSV has
a spherical shape, and the viral particle has a diameter of 186 nm with glycoprotein
spikes that protrude from each virion, making their full diameter 225 nm (Banerjee
et al., 2020). It has been estimated that at least 66 percent of individuals under the age
of 50 years have been infected with HSV- 1, which is responsible for cold sores (Looker
et al., 2020). HSV has an enormous impact on the global health of individuals ranging
from mild infections of the mouth (i.e., cold sores), eye (i.e., cornea), and genitals to
severe cases of encephalitis and pneumonia that can be fatal (Jellinge et al., 2021; Stahl
& Mailles, 2019). HSV- 1 and HSV- 2 infection leading to genital lesions and ulcers is
more common in females compared to males (2:1) (Looker & Garnett, 2005; Looker
et al., 2020). ere is currently no cure for HSV infection (Whitley & Hook, 2022).
Transmission of HSV
Pathways of transmission
e transmission of HSV involves direct physical contact with an infected individual, which can quickly establish acute infections in the skin. It should be noted
that most sexual transmissions occur during asymptomatic shedding (Schier et al.,
2014). Transmission of HSV can occur in the following ways:
• Sexual activity (oral sex, kissing, sexual intercourse) (Johnston, 2022; Looker &
Garnett, 2005)
Guy D. Eslick,
Neurocognitive and Neuropsychiatric Medicine
© Oxford University Press 2024. DOI: 10.1093/ oso/ 9780192870414.003.0003
Herpes Simplex Viruses 25
• Zoonotic contact (animal bite) (Lyra et al., 2019)
• Organ transplantation (Macesic et al., 2017)
• Vaginal seeding (Huynh et al., 2018)
• Direct contact with saliva (Mayer et al., 2020)
• Direct contact with semen (Torres et al., 2015)
• Vertical transmission during childbirth (Hammad & Konje, 2021).
e cell cycle for HSV is complex and will not be discussed in detail in this chapter,
but please see Figure 2.1 for a summary of the process.
Translation
Budding
Transport to
the periphery
Receptor
Transport on
microtubules
Binding
Translation
Transcription
IE genes
VP16
Fusion
Cytoplasm
Translation
Transcription
E genes
Nucleus
Transcription
L genes
DNA encapsidationDNA replication
Figure 2.1 HSV cell cycle. (1) HSV glycoprotein D or B interacts with specific cellular receptors
leading to fusion at the plasma membrane (2) following endocytosis (not shown in this figure).
Upon fusion, the capsid is released to the cytoplasm with some attached tegument proteins,
while other tegument proteins like VP16 separate from the capsid. (3) The capsid travels to
the cell nucleus using microtubuli due to the interaction between UL36 and motor proteins.
The linear DNA enters the nucleus. (4) The tegument protein VP16 enters the nucleus together
with HCF- 1 and Oct- 1 and starts transcription of IE genes. (5) The IE genes are translated and
participate in the transcription of E genes (6), which take part in the replication of the viral
genome (8). Once there are suicient copies of viral genomes, the products of the L genes
facilitate DNA encapsidation (11). The mature, DNA- containing capsids (C capsids) leave
the nucleus through an envelopment– de- envelopment process and acquire tegument and
envelope (not shown) prior to cellular egress (14).
Source: Zhu, S. & Viejo- Borbolla, A. 2021. Pathogenesis and virulence of herpes simplex virus. Virulence,
12, 2670– 2702. https:// doi.org/ 10.1080/ 21505 594.2021.1982 373. https:// crea tive comm ons.org/ licen ses/
by/ 4.0/
Infectious Disease and Neurocognition
Ribosome
terochromatin
herpesvirus
Latent
Viral latency
HSV is a very successful (i.e., highly prevalent) infection because of its ability to
establish latency and reactivate at another point in time, especially in those who
are immunocompromised (Macesic et al., 2017). The latency process is complex, a summary of which is shown in Figure 2.2 (Schwartz & Stern- Ginossar,
2023). This is a dynamic area of infectious disease research and impacts
coinfection with other viral infections such as human immunodeficiency virus
(Desai & Kulkarni, 2015) and with vaccine development (Preda et al., 2023).
(a)
Host cell
Latent
herpesvirus
DNA
(d)
Latent
chromatin
(e)
Heterochromatin He
(f)
Block in
translation
Histone
(b) (c)
Host cell
chromosome
herpesvirus
H3K9 and H3K27
trimethylation
Repressed
heterochromatin
state
Insulator
(boundary)
Herpesvirus
miRNA
Viral or
host RNA
methylation
RNA
degradation
Tethering
protein
Latent
DNA
H3K4
Active euchromatin
Euchromatin
H3K9
acetylation
state
herpesvirus
DNA
Long
noncoding
RNA
Lytic gene RNA
antisense to long
noncoding RNA
Figure 2.2 Features of herpesvirus latency. (a, b) Latent herpesvirus genomes are maintained
in the nuclei of cells as circular episomes (a) and in dividing cells, the viruses express proteins
during cell division that partition the episomes to daughter cells (b). (c) Alphaherpesviruses
encode long noncoding viral RNAs during latency that are transcribed antisense to viral
genes expressed during lytic infection. (d) Latent herpesvirus DNA genomes are associated
with histone proteins; genes normally expressed during virus lytic replication are silenced
by methylation or other modifications of their histone tails during latency. (e) Chromatin
insulators containing DNA sequences and the corresponding DNA- binding proteins and
chromatin- modifying proteins act to separate regions of active euchromatin and repressed
heterochromatin to regulate latency. (f) Herpesvirus microRNAs (miRNAs) produced during
latency degrade or inhibit expression of virus lytic genes or host cell genes.
Source: Cohen, J. I. 2020. Herpesvirus latency. J Clin Invest,
https:// crea tive comm ons.org/ licen ses/ by/ 4.0/
Herpes Simplex Viruses 27
Vertical transmission
Vertical transmission of HSV can be acquired by an infant at three dierent potential time points. e rst is in utero, which accounts for about 5 percent of cases; the
second is in the peripartum phase, which is where the majority of transmission occurs (approximately 85 percent); and the third is in the postnatal period, which accounts for approximately 10 percent of infections (Hammad & Konje, 2021). While
neonatal HSV is rare, these infections can have a substantial morbidity and mortality (Donda et al., 2019; Lopez- Medina et al., 2015), particularly with disseminated
central nervous system disease (Teutsch et al., 2023).
e Australian Paediatric Surveillance Unit (APSU) has been conducting annual
national surveillance on neonatal and infant HSV for 26 years (Teutsch et al., 2023).
In 2022, the APSU had ten conrmed cases of neonatal HSV (age: 1– 21 days), with
30 percent having disseminated disease, 30 percent with skin– eye– mucous membrane disease, and 60 percent with central nervous system disease. e HSV type
was 50 percent HSV- 1 and 50 percent HSV- 2.
In 2022, the annual incidence of neonatal HSV infection was 3.38/ 100,000 live
births (95 percent condence interval (CI): 1.82– 6.28). With approximately 300,000
births annually in Australia (Teutsch et al., 2023), neonatal HSV is a rare condition.
Neurocognitive and neuropsychiatric function
Pediatric population
Congenital HSV infection can result in clinically important neurological complications, such as meningoencephalitis, microcephaly, hydranencephaly, and intracranial calcications (Sauerbrei & Wutzler, 2007). It is critical aer diagnosis that
antiretroviral treatment commence immediately; otherwise, the mortality rate can
be as high as 60 percent (Muller, 2017), and even with early use of acyclovir treatment, there may still be serious disability.
Neurological deficits
A recent systematic review and meta- analysis aimed to determine the prevalence
and types of neurological complications aer developing HSV- associated encephalitis using the PRISMA guidelines (Rocha et al., 2023). e authors searched
databases including MEDLINE, Embase, SciELO, LILACS, Cochrane, CINAHL,
PsycINFO, and Web of Science. Only studies of children with conrmed HSV infection were included in the study. Neurological complications were dened as
(1) seizures (e.g., convulsions, focal or generalized epilepsy), (2) motor disabilities
(e.g., focal decit, hemiplegia, ataxia), (3) visual impairments (e.g., reduced visual